These studies are directed toward determining the molecular lesion which is responsible for decreased beta globin synthesis in patients with homozygous beta thalassemia. Current evidence indicates that there is a quantitative deficiency of beta globin mRNA in reticulocytes. This might result because of defective transcription of the globin genes in chromatin, inefficient processing and therefore accumulation of the globin mRNA during erythroid maturation, or reduced stability of the final globin mRNA product. Our studies are directed toward determining, in individual patients, which of these mechanisms is responsible for reduced beta globin mRNA. Thus the spectrum of molecular defects in beta thalassemia will be determined and ultimately the alterations in mRNA synthesis or metabolism will be correlated with the nucleotide sequence of molecules containing beta globin mRNA sequences.